{"title":"Exendin-4 imaging based on gastrointestinal GLP-1R targets for IBD diagnosis and efficacy assessment","authors":"Xiaochen Li, Yang Liu, Zizhen Zhang, Wangxi Hai, Yu Pan, Yifan Zhang","doi":"10.1007/s00259-025-07197-z","DOIUrl":null,"url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>Diagnosis of inflammatory bowel disease (IBD) involves history-taking and invasive procedures that primarily evaluate localized intestinal structures. Notably, glucagon-like peptide 1 (GLP-1) and its receptor (GLP-1R) have been established as potent participants in various inflammatory diseases. This study aimed to investigate the potential of molecular imaging targeting GLP-1R in the study of gastrointestinal physiology and disease.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Using dextran sulfate sodium (DSS)-induced IBD rats (<i>n</i> = 6), changes in GLP-1R expression in the gastrointestinal tract before and after DSS induction were determined by quantitative micro-PET/CT. Dynamic changes in GLP-1R expression after liraglutide treatment were also assessed in IBD rats. Transcription of GLP-1R and inflammatory factors in duodenal and colonic tissues were measured and subjected to correlation analysis.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>In normal rats, GLP-1R was highly concentrated in the proximal duodenum, with a higher distribution density near the distal end of the colonic segment. Proximal duodenal uptake of [<sup>68</sup>Ga]Ga-NOTA-MAL-Cys<sup>39</sup>-exendin-4 was significantly increased after DSS induction compared with controls. The increased colonic uptake closely correlated with the histopathologic score of epithelial injury. In IBD rats treated with liraglutide, proximal duodenal uptake was reduced. In addition, Western blotting and quantitative PCR confirmed changes in GLP-1R expression during disease progression.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>These findings underscore the role of molecular imaging in assessing dynamic changes in GLP-1R expression and its potential for improving diagnostic and therapeutic strategies for gastrointestinal disorders like IBD. It supports using Brunner’s glands as a key site to observe GLP-1R expression, advancing research on the GLP-1R/GLP-1RA axis in complex gastrointestinal conditions.</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":"6 1","pages":""},"PeriodicalIF":8.6000,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Nuclear Medicine and Molecular Imaging","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00259-025-07197-z","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING","Score":null,"Total":0}
引用次数: 0
Abstract
Purpose
Diagnosis of inflammatory bowel disease (IBD) involves history-taking and invasive procedures that primarily evaluate localized intestinal structures. Notably, glucagon-like peptide 1 (GLP-1) and its receptor (GLP-1R) have been established as potent participants in various inflammatory diseases. This study aimed to investigate the potential of molecular imaging targeting GLP-1R in the study of gastrointestinal physiology and disease.
Methods
Using dextran sulfate sodium (DSS)-induced IBD rats (n = 6), changes in GLP-1R expression in the gastrointestinal tract before and after DSS induction were determined by quantitative micro-PET/CT. Dynamic changes in GLP-1R expression after liraglutide treatment were also assessed in IBD rats. Transcription of GLP-1R and inflammatory factors in duodenal and colonic tissues were measured and subjected to correlation analysis.
Results
In normal rats, GLP-1R was highly concentrated in the proximal duodenum, with a higher distribution density near the distal end of the colonic segment. Proximal duodenal uptake of [68Ga]Ga-NOTA-MAL-Cys39-exendin-4 was significantly increased after DSS induction compared with controls. The increased colonic uptake closely correlated with the histopathologic score of epithelial injury. In IBD rats treated with liraglutide, proximal duodenal uptake was reduced. In addition, Western blotting and quantitative PCR confirmed changes in GLP-1R expression during disease progression.
Conclusion
These findings underscore the role of molecular imaging in assessing dynamic changes in GLP-1R expression and its potential for improving diagnostic and therapeutic strategies for gastrointestinal disorders like IBD. It supports using Brunner’s glands as a key site to observe GLP-1R expression, advancing research on the GLP-1R/GLP-1RA axis in complex gastrointestinal conditions.
期刊介绍：
The European Journal of Nuclear Medicine and Molecular Imaging serves as a platform for the exchange of clinical and scientific information within nuclear medicine and related professions. It welcomes international submissions from professionals involved in the functional, metabolic, and molecular investigation of diseases. The journal's coverage spans physics, dosimetry, radiation biology, radiochemistry, and pharmacy, providing high-quality peer review by experts in the field. Known for highly cited and downloaded articles, it ensures global visibility for research work and is part of the EJNMMI journal family.
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